THE INVOLVEMENT OF NITRIC-OXIDE IN THE OVULATORY PROCESS IN THE RAT

Nitric Oxide (NO) is now recognized as a mediator of several biological functions. In the present study we examined the effects of NO synthase (NOS) inhibitors on the ovulatory process in vivo, and whether this effect can be reversed by a NO generator. Immature eCG-hCG treated rats were injected intraperitonealy tip) or unilaterally into the periovarian sac (intrabursal injection; ib) with inhibitors of the inducible form of NOS. Aminoguanidine (AG) suppressed ovulation in a dose-dependent manner, reaching a 54% inhibition at a dose of 20 mg/kg when injected ip (p<0.001 vs. saline control). Likewise, local ib administration inhibited ovulation from the treated ovary; thus a dose of 2 mg/kg resulted in 48% inhibition, as compared to the contralateral ovary (p<0.01). Similar results were obtained whether AG was administered 2 h prior to the stimulation of ovulation by hCG or deferred up to 4 h afterwards. An additional NOS inhibitor, N-G-methyl-L-arginine (L-NMA) suppressed ovulation, albeit to a lower extent. Intrabursal administration of L-NMA (0.1 and 1 mg/kg) resulted in 34% and 32% inhibition, respectively (p<0.05 vs, the saline treated control). The same doses of N-G-methyl-D-arginine (D-NMA) did not inhibit ovulation significantly compared to the saline treated control. When sodium nitroprusside (0.5 mg/kg), a NO generator, was injected concomitantly with AG, it completely reversed its inhibitory action on ovulation. Thus, we have demonstrated the ability of NOS inhibitors to suppress hCG-induced ovulation in the rat in vivo. The specificity of this effect is confirmed by the ability of a NO generator to reverse the inhibitory action of AG. In conclusion, the ovarian NO/NOS system seems to be necessary for follicle rupture during ovulation.